全文获取类型
收费全文 | 2052篇 |
免费 | 183篇 |
国内免费 | 80篇 |
专业分类
耳鼻咽喉 | 19篇 |
儿科学 | 46篇 |
妇产科学 | 21篇 |
基础医学 | 824篇 |
口腔科学 | 13篇 |
临床医学 | 100篇 |
内科学 | 319篇 |
皮肤病学 | 25篇 |
神经病学 | 65篇 |
特种医学 | 23篇 |
外科学 | 127篇 |
综合类 | 178篇 |
预防医学 | 172篇 |
眼科学 | 12篇 |
药学 | 250篇 |
中国医学 | 35篇 |
肿瘤学 | 86篇 |
出版年
2024年 | 4篇 |
2023年 | 33篇 |
2022年 | 57篇 |
2021年 | 134篇 |
2020年 | 99篇 |
2019年 | 101篇 |
2018年 | 105篇 |
2017年 | 89篇 |
2016年 | 99篇 |
2015年 | 120篇 |
2014年 | 217篇 |
2013年 | 160篇 |
2012年 | 155篇 |
2011年 | 194篇 |
2010年 | 138篇 |
2009年 | 113篇 |
2008年 | 123篇 |
2007年 | 88篇 |
2006年 | 71篇 |
2005年 | 42篇 |
2004年 | 29篇 |
2003年 | 25篇 |
2002年 | 12篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 12篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1990年 | 5篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有2315条查询结果,搜索用时 31 毫秒
41.
42.
Qiang Fu Le Xu Yiwei Wang Qi Jiang Zheng Liu Junyu Zhang Quan Zhou Han Zeng Shanyou Tong Tao Wang Yangyang Qi Baoying Hu Hangcheng Fu Huyang Xie Lin Zhou Yuan Chang Yu Zhu Bo Dai Jiejie Xu 《European urology》2019,75(5):752-763
Background
Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.Objective
To seek a potential therapeutic target in glutamine-addicted ccRCC.Design, setting, and participants
Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells.Outcome measurements and statistical analysis
Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses.Results and limitations
We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR] = 2.04, cancer-specific survival [CSS] HR = 2.95; all p < 0.001) and Shanghai (OS HR = 2.07, CSS HR = 3.92; all p < 0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor β expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells.Conclusions
Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC.Patient summary
In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23–high patients had significantly poorer survival than IL-23–low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors. 相似文献43.
The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food. 相似文献
44.
46.
蛋白激酶A(PKA)是由1个调节亚基(R亚基)二聚体和两个催化亚基(C亚基)组成的四聚体,全酶无活性。R亚基有RⅠα、RⅠβ、RⅡα和RⅡβ4种亚型,分别具有不同的理化性质。RⅡβ亚基氨基端包含1个二聚化/对接结构域,PKA通过此结构域与腺苷酸激酶锚定蛋白结合锚定于细胞的特定位点。羧基端是两个串联的高度保守的环核苷酸结构域,与PKA全酶解聚以及激活有关。两个RC异二聚体通过RⅡβ亚基中的β4~β5环相锚定。细胞质中存在足够的Mg ATP时将导致RⅡβ亚基自身磷酸化。RⅡβ在特定组织表达,主要表达于内分泌腺、脑和脂肪组织。生物信息学分析表明,RⅡβ与其他R亚基的序列有很大差别,只有大约50%的序列相同,提示RⅡβ可能具有不同的生物学功能。因此,目前对PKA RⅡβ的功能及其作用机制的研究已逐渐成为热点。 相似文献
47.
48.
目的 检测老年原发免疫性血小板减少症(ITP)患者治疗前后T淋巴细胞亚群的动态变化, 探讨其在ITP发生发展中的作用。方法 采用流式细胞术测定ITP患者治疗前后及正常对照组外周血T淋巴细胞亚群的水平。结果 ITP患者治疗前后T淋巴细胞绝对值、CD3+、CD4+、CD8+、CD4+CD25+T淋巴细胞比例及CD4+/CD8+比值分别为(0.83±0.16)vs(1.74±0.36)、(71.71±1.07)% vs(72.69±1.35)%、(41.78±0.71)% vs(42.46±1.20)%、(29.67±0.97)% vs(28.56±1.75)%、(8.76±0.56)% vs(9.39±1.26)%、(1.42±0.07)vs(1.49±0.13), CD8+T淋巴细胞比例治疗后显著降低, 其余均显著升高, 差异有统计学意义(P<0.05)。结论 T淋巴细胞亚群的异常改变, 破坏自身免疫, 与病情相关, 可指导临床治疗, 并作为评估预后的参考指标。 相似文献
49.
目的 观察正常甲状腺及Graves病(GD)患者甲状腺组织中免疫调节T淋巴细胞的比例.方法 采用流式细胞术分别检测20例正常甲状腺及9例GD患者甲状腺中Treg细胞、Th1细胞、Th2细胞比例,并与外周血进行对比.结果 外周血、正常甲状腺、GD甲状腺中Treg细胞比例分别为1.79±0.43%、17.07±10.16%、20.87±13.26%,Th1细胞比例分别为14.45±2.46%、17.28±3.02%、8.62±1.88%,Th2细胞比例分别为1.44±0.31%、1.78±0.55%、6.87±3.27%.与外周血相比,正常甲状腺及GD甲状腺中Treg细胞比例明显增高(P<0.01),与正常甲状腺相比,GD甲状腺中Th1细胞比例明显降低(P<0.05),Th2细胞比例明显升高(P<0.01).结论 甲状腺组织局部存在着数量明显增多的Treg细胞,GD患者的甲状腺中存在Th1/Th2细胞失衡. 相似文献
50.
With the explosive economic growth and social development, China’s regulatory system of
occupational health and safety now faces more and more challenges. This article reviews
the history of regulatory system of occupational health and safety in China, as well as
the current reform of this regulatory system in the country. Comprehensive, a range of
laws, regulations and standards that promulgated by Chinese government, duties and
responsibilities of the regulatory departments are described. Problems of current
regulatory system, the ongoing adjustments and changes for modifying and improving
regulatory system are discussed. The aim of reform and the incentives to drive forward
more health and safety conditions in workplaces are also outlined. 相似文献